Cell-fate conversion of lymphoid-committed progenitors by instructive actions of cytokines

The primary role of cytokines in haemato-lymphopoiesis is thought to be the regulation of cell growth and survival. But the instructive action of cytokines in haematopoiesis has not been well addressed. Here we show that a clonogenic common lymphoid progenitor, a bone marrow-resident cell that gives rise exclusively to lymphocytes (T, B and natural killer cells), can be redirected to the myeloid lineage by stimulation through exogenously expressed interleukin (IL)-2 and GM-CSF (granulocyte/macrophage colony-stimulating factor) receptors. Analysis of mutants of the beta-chain of the IL-2 receptor revealed that the granulocyte- and monocyte-differentiation signals are triggered by different cytoplasmic domains, showing that the signalling pathway(s) responsible for these unique developmental outcomes are separable. Finally, we show that the endogenous myelomonocytic cytokine receptors for GM-CSF and macrophage colony-stimulating factor (M-CSF) are expressed at low to moderate levels on the more primitive haematopoietic stem cells, are absent on common lymphoid progenitors, and are upregulated after myeloid lineage induction by IL-2. We conclude that cytokine signalling can regulate cell-fate decisions and propose that a critical step in lymphoid commitment is downregulation of cytokine receptors that drive myeloid cell development.     

Antibiotic resistance is ancient

The discovery of antibiotics more than 70 years ago initiated a period of drug innovation and implementation in human and animal health and agriculture. These discoveries were tempered in all cases by the emergence of resistant microbes. This history has been interpreted to mean that antibiotic resistance in pathogenic bacteria is a modern phenomenon; this view is reinforced by the fact that collections of microbes that predate the antibiotic era are highly susceptible to antibiotics. Here we report targeted metagenomic analyses of rigorously authenticated ancient DNA from 30,000-year-old Beringian permafrost sediments and the identification of a highly diverse collection of genes encoding resistance to β-lactam, tetracycline and glycopeptide antibiotics. Structure and function studies on the complete vancomycin resistance element VanA confirmed its similarity to modern variants. These results show conclusively that antibiotic resistance is a natural phenomenon that predates the modern selective pressure of clinical antibiotic use.     

Simultaneous teleseismic and geodetic observations of the stick-slip motion of an Antarctic ice stream

Long-period seismic sources associated with glacier motion have been recently discovered, and an increase in ice flow over the past decade has been suggested on the basis of secular changes in such measurements. Their significance, however, remains uncertain, as a relationship to ice flow has not been confirmed by direct observation. Here we combine long-period surface-wave observations with simultaneous Global Positioning System measurements of ice displacement to study the tidally modulated stick-slip motion of the Whillans Ice Stream in West Antarctica. The seismic origin time corresponds to slip nucleation at a region of the bed of the Whillans Ice Stream that is likely stronger than in surrounding regions and, thus, acts like an 'asperity' in traditional fault models. In addition to the initial pulse, two seismic arrivals occurring 10-23 minutes later represent stopping phases as the slip terminates at the ice stream edge and the grounding line. Seismic amplitude and average rupture velocity are correlated with tidal amplitude for the different slip events during the spring-to-neap tidal cycle. Although the total seismic moment calculated from ice rigidity, slip displacement, and rupture area is equivalent to an earthquake of moment magnitude seven (M(w) 7), seismic amplitudes are modest (M(s) 3.6-4.2), owing to the source duration of 20-30 minutes. Seismic radiation from ice movement is proportional to the derivative of the moment rate function at periods of 25-100 seconds and very long-period radiation is not detected, owing to the source geometry. Long-period seismic waves are thus useful for detecting and studying sudden ice movements but are insensitive to the total amount of slip.     

青藏高原东部及邻区地块现今运动特征

青藏高原东部及邻区为典型的大陆地壳变形区.根据GPS监测结果,得出了欧亚参考框架的运动速度场;采用刚性假设下最小二乘法,对地块现今运动进行了研究.GPS监测结果表明:柴达木地块、甘青地块、华南地块、川滇地块、印支地块运动速率分别为(11.95士2.89)mm/a,(11.86士2.32)mm/a,(7.83士2.08)mm/a,(13.18±2.43)mm/a,(6.45士1.95)mm/a;运动方向分别为61.1°,93.8°,113.1°,134.8°,141.6°;旋转速率分别为2.91×10-9rad/a,6.91×10-9rad/a,0.38×10-9rad/a,2.15×10-9rad/a,1.45×10-9rad/a.柴达木地块、甘青地块、川滇地块活动性较强,而华南地块、印支地块活动性较弱,属于稳定地块;各块体围绕东喜马拉雅构造结呈顺时针旋转.地块规律性运动特征与印度板块向北俯冲、推挤有作密切关系;而地块的差异运动则与总体构造应力条件下远程边缘效应及地块之间相互作用有关.     

A distal enhancer and an ultraconserved exon are derived from a novel retroposon

Hundreds of highly conserved distal cis-regulatory elements have been characterized so far in vertebrate genomes. Many thousands more are predicted on the basis of comparative genomics. However, in stark contrast to the genes that they regulate, in invertebrates virtually none of these regions can be traced by using sequence similarity, leaving their evolutionary origins obscure. Here we show that a class of conserved, primarily non-coding regions in tetrapods originated from a previously unknown short interspersed repetitive element (SINE) retroposon family that was active in the Sarcopterygii (lobe-finned fishes and terrestrial vertebrates) in the Silurian period at least 410 million years ago (ref. 4), and seems to be recently active in the 'living fossil' Indonesian coelacanth, Latimeria menadoensis. Using a mouse enhancer assay we show that one copy, 0.5 million bases from the neuro-developmental gene ISL1, is an enhancer that recapitulates multiple aspects of Isl1 expression patterns. Several other copies represent new, possibly regulatory, alternatively spliced exons in the middle of pre-existing Sarcopterygian genes. One of these, a more than 200-base-pair ultraconserved region, 100% identical in mammals, and 80% identical to the coelacanth SINE, contains a 31-amino-acid-residue alternatively spliced exon of the messenger RNA processing gene PCBP2 (ref. 6). These add to a growing list of examples in which relics of transposable elements have acquired a function that serves their host, a process termed 'exaptation', and provide an origin for at least some of the many highly conserved vertebrate-specific genomic sequences.     

The Cenozoic palaeoenvironment of the Arctic Ocean

The history of the Arctic Ocean during the Cenozoic era (0-65 million years ago) is largely unknown from direct evidence. Here we present a Cenozoic palaeoceanographic record constructed from >400 m of sediment core from a recent drilling expedition to the Lomonosov ridge in the Arctic Ocean. Our record shows a palaeoenvironmental transition from a warm 'greenhouse' world, during the late Palaeocene and early Eocene epochs, to a colder 'icehouse' world influenced by sea ice and icebergs from the middle Eocene epoch to the present. For the most recent approximately 14 Myr, we find sedimentation rates of 1-2 cm per thousand years, in stark contrast to the substantially lower rates proposed in earlier studies; this record of the Neogene reveals cooling of the Arctic that was synchronous with the expansion of Greenland ice (approximately 3.2 Myr ago) and East Antarctic ice (approximately 14 Myr ago). We find evidence for the first occurrence of ice-rafted debris in the middle Eocene epoch (approximately 45 Myr ago), some 35 Myr earlier than previously thought; fresh surface waters were present at approximately 49 Myr ago, before the onset of ice-rafted debris. Also, the temperatures of surface waters during the Palaeocene/Eocene thermal maximum (approximately 55 Myr ago) appear to have been substantially warmer than previously estimated. The revised timing of the earliest Arctic cooling events coincides with those from Antarctica, supporting arguments for bipolar symmetry in climate change.     

Wnt-Ryk signalling mediates medial-lateral retinotectal topographic mapping

Computational modelling has suggested that at least two counteracting forces are required for establishing topographic maps. Ephrin-family proteins are required for both anterior-posterior and medial-lateral topographic mapping, but the opposing forces have not been well characterized. Wnt-family proteins are recently discovered axon guidance cues. We find that Wnt3 is expressed in a medial-lateral decreasing gradient in chick optic tectum and mouse superior colliculus. Retinal ganglion cell (RGC) axons from different dorsal-ventral positions showed graded and biphasic response to Wnt3 in a concentration-dependent manner. Wnt3 repulsion is mediated by Ryk, expressed in a ventral-to-dorsal decreasing gradient, whereas attraction of dorsal axons at lower Wnt3 concentrations is mediated by Frizzled(s). Overexpression of Wnt3 in the lateral tectum repelled the termination zones of dorsal RGC axons in vivo. Expression of a dominant-negative Ryk in dorsal RGC axons caused a medial shift of the termination zones, promoting medially directed interstitial branches and eliminating laterally directed branches. Therefore, a classical morphogen, Wnt3, acting as an axon guidance molecule, plays a role in retinotectal mapping along the medial-lateral axis, counterbalancing the medial-directed EphrinB1-EphB activity.